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16 pages, 293 KB  
Perspective
Management of Patients with Nickel Hypersensitivity Undergoing Patent Foramen Ovale Closure
by Anastasios Apostolos, Stamatios Gregoriou, Maria Drakopoulou, Georgios Trantalis, Aikaterini Tsiogka, Nikolaos Ktenopoulos, Panayotis K. Vlachakis, Paschalis Karakasis, Andreas Synetos, Georgios Tsivgoulis, Alexander Stratigos, Konstantinos Tsioufis and Konstantinos Toutouzas
J. Clin. Med. 2025, 14(21), 7540; https://doi.org/10.3390/jcm14217540 (registering DOI) - 24 Oct 2025
Abstract
Patent foramen ovale (PFO) is implicated in cryptogenic stroke and other clinical syndromes, with transcatheter closure demonstrating superiority over medical therapy in selected patients. Most closure devices are composed of nitinol, a nickel–titanium alloy, raising concerns in individuals with nickel hypersensitivity, one of [...] Read more.
Patent foramen ovale (PFO) is implicated in cryptogenic stroke and other clinical syndromes, with transcatheter closure demonstrating superiority over medical therapy in selected patients. Most closure devices are composed of nitinol, a nickel–titanium alloy, raising concerns in individuals with nickel hypersensitivity, one of the most prevalent contact allergies worldwide. Although typically manifesting as localized dermatitis, nickel allergy has been associated with systemic reactions after device implantation, including chest pain, palpitations, migraines, dyspnea, and cutaneous eruptions. Recent evidence indicates that nickel-sensitive patients experience a significantly higher incidence of post-procedural device-related symptoms. Nevertheless, severe reactions remain rare, and the benefits of PFO closure generally outweigh the risks. The predictive value of pre-implantation patch testing remains uncertain, and the lack of nickel-free alternatives constrains device selection. Management strategies are empirical, relying on symptomatic treatment with corticosteroids, antihistamines, or device explantation in refractory cases. Future research should focus on elucidating the pathophysiology of nickel-induced hypersensitivity in cardiovascular implants, improving diagnostic algorithms, and developing biocompatible, nickel-free devices. A multidisciplinary approach involving cardiologists, dermatologists, and allergists is essential to optimize outcomes in this complex subset of patients. Full article
(This article belongs to the Section Dermatology)
13 pages, 845 KB  
Article
Integrating Quality of Life Metrics into Head and Neck Cancer Treatment Planning: Evidence and Implications
by Paula Luiza Bejenaru, Gloria Simona Berteșteanu, Raluca Grigore, Ruxandra Ioana Nedelcu-Stancalie, Teodora Elena Schipor-Diaconu, Simona Andreea Rujan, Bianca Petra Taher, Bogdan Popescu, Irina Doinița Popescu, Alexandru Nicolaescu, Anca Ionela Cîrstea, Catrinel Beatrice Simion-Antonie and Șerban Gabriel Vifor Berteșteanu
J. Otorhinolaryngol. Hear. Balance Med. 2025, 6(2), 19; https://doi.org/10.3390/ohbm6020019 (registering DOI) - 24 Oct 2025
Abstract
Background/Objectives: Head and neck cancers significantly affect patients’ functional and psychosocial well-being. Multidisciplinary tumor boards have a central role in optimizing treatment strategies, but the relationship between tumor characteristics, comorbidities, and quality of life (QoL) remains insufficiently explored. Methods: We conducted a [...] Read more.
Background/Objectives: Head and neck cancers significantly affect patients’ functional and psychosocial well-being. Multidisciplinary tumor boards have a central role in optimizing treatment strategies, but the relationship between tumor characteristics, comorbidities, and quality of life (QoL) remains insufficiently explored. Methods: We conducted a retrospective study of 94 patients with head and neck cancers evaluated by the oncology committee of Coltea Clinical Hospital in 2024. QoL was assessed post-surgery using the EORTC QLQ-C30 and H&N35 questionnaires. Descriptive statistics, non-parametric tests, correlations, and multivariate regression analyses were performed to examine associations between clinical variables and QoL outcomes. Results: The cohort comprised 82 men (87.2%) and 12 women (12.8%), with a mean age of 61.5 ± 9.8 years. The most common tumor site was the larynx (43.6%). Global QoL was low (mean = 42.3, SD = 11.7), and fatigue scores were high (mean = 61.5, SD = 13.5). All EORTC domains showed non-normal distributions (Shapiro–Wilk, p < 0.05). Kruskal–Wallis analysis revealed significantly lower QoL scores in patients with metastatic adenopathy with aunknown primary (p = 0.03). Spearman’s correlation indicated a moderate negative association between Charlson Comorbidity Index and QoL (r = −0.38, p = 0.01). Multivariate regression confirmed comorbidities (β = −2.5, p = 0.02) and tumor type (metastatic adenopathy, β = −8.0, p = 0.04) as independent predictors of reduced QoL. Conclusions: Patients with advanced disease and higher comorbidity burden experience significantly poorer QoL after head and neck cancer surgery. Tumor board decisions facilitate individualized treatment planning; however, systematic integration of QoL metrics is essential to optimize both oncological and functional outcomes. Full article
(This article belongs to the Section Head and Neck Surgery)
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21 pages, 1196 KB  
Review
Understanding Atopic Dermatitis: Pathophysiology and Management Strategies
by Heng Chai, Wing Sum Siu, Hui Ma and Yuzhen Li
Biomolecules 2025, 15(11), 1500; https://doi.org/10.3390/biom15111500 - 24 Oct 2025
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by itching, redness, and dryness, significantly impacting the quality of life of affected individuals. With a rising prevalence across diverse demographics, understanding AD is crucial due to its systemic nature and association with [...] Read more.
Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by itching, redness, and dryness, significantly impacting the quality of life of affected individuals. With a rising prevalence across diverse demographics, understanding AD is crucial due to its systemic nature and association with comorbidities such as asthma and allergic rhinitis, as well as its psychosocial implications. The pathophysiology of AD involves a complex interplay of genetic predispositions and environmental triggers, leading to dysbiosis and increased susceptibility to superinfection. Clinically, AD manifests variably across age groups, with distinct presentations in pediatric and adult populations. Diagnosis is primarily based on clinical assessment criteria, supplemented by differential diagnoses and, when necessary, skin tests for allergies. Current management strategies encompass topical therapies, including moisturizers, corticosteroids, and calcineurin inhibitors, alongside systemic treatments such as antihistamines, immunosuppressants, and biologics. Lifestyle modifications, including trigger avoidance and effective skin care routines, are essential components of comprehensive care. Emerging novel therapies targeting specific biomarkers are currently under investigation in clinical trials, offering promising avenues for more effective management. However, challenges remain in optimizing treatment protocols and addressing the multifaceted nature of AD. In conclusion, this review highlights the need for continued research and awareness regarding atopic dermatitis. A multidisciplinary approach to management is essential to enhance patient outcomes and address the complexities of this prevalent and impactful condition. Full article
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24 pages, 352 KB  
Review
Sexual Dysfunction in Traumatic Brain Injury: A Narrative Review and Call for Multidisciplinary Framework
by Ioannis Mavroudis, Foivos Petridis, Dimitrios Kazis, Gabriel Dăscălescu, Alin Ciobica, Ciprian Ilea, Sorana Caterina Anton and Emil Anton
Life 2025, 15(11), 1659; https://doi.org/10.3390/life15111659 - 23 Oct 2025
Abstract
Background: Sexual dysfunction (SD) is a common yet under-recognized consequence of traumatic brain injury (TBI), with significant implications for physical health, psychological well-being, interpersonal relationships and social reintegration. Although TBI research has largely focused on cognitive, motor and behavioral outcomes, the impact of [...] Read more.
Background: Sexual dysfunction (SD) is a common yet under-recognized consequence of traumatic brain injury (TBI), with significant implications for physical health, psychological well-being, interpersonal relationships and social reintegration. Although TBI research has largely focused on cognitive, motor and behavioral outcomes, the impact of SD remains insufficiently addressed in both clinical practice and rehabilitation programs. Objectives: This review aims to synthesize current evidence on the prevalence, mechanisms and management of SD following TBI, while emphasizing the importance of gender-sensitive and multidisciplinary approaches to care. Methods: A narrative review was conducted by searching PubMed, Scopus and Web of Science for English-language articles published between 2000 and 2025 using combinations of the following keywords: traumatic brain injury, sexual dysfunction, neuroendocrine dysfunction, psychological sequelae and rehabilitation. Priority was given to peer-reviewed clinical studies, systematic reviews and expert consensus guidelines that addressed neurological, endocrine, cognitive, psychological and social aspects of SD in TBI survivors. Exclusion criteria included case reports with insufficient clinical detail and non-peer-reviewed sources. Articles were screened for relevance to both pathophysiological mechanisms and therapeutic strategies. Results: The etiology of post-TBI SD is multifactorial, involving direct neurological injury, hypothalamic–pituitary dysfunction, emotional and cognitive impairments, as well as psychological challenges such as stigma and relationship strain. Men and women may present distinct symptom profiles; for instance, men more frequently report erectile dysfunction and hypogonadism, whereas women more commonly experience challenges with arousal, lubrication and psychological stress. Effective interventions include pharmacotherapy, hormone replacement therapy, psychotherapy and rehabilitative approaches designed to restore intimacy and quality of life. Optimal outcomes are achieved through multidisciplinary collaboration among neurology, endocrinology, psychiatry, psychology and rehabilitation medicine. Conclusions: Sexual dysfunction should be recognized as a critical component of TBI sequelae rather than a secondary concern. Routine screening, gender-sensitive assessment and the integration of individualized, multidisciplinary care pathways are essential to improving patient outcomes. Advancing clinical awareness and standardization in this area holds the potential to significantly enhance the holistic recovery and reintegration of TBI survivors. Full article
(This article belongs to the Section Medical Research)
11 pages, 1153 KB  
Case Report
Partial Androgen Insensitivity Syndrome and Congenital Adrenal Hyperplasia—A Case Report of the Coexistence of Two Rare Diseases in One Patient
by Mariola Krzyścin, Agnieszka Brodowska, Gabriela Furtak, Dominika Pietrzyk, Katarzyna Zając, Bartosz Oder, Adam Przepiera and Elżbieta Sowińska-Przepiera
Reports 2025, 8(4), 212; https://doi.org/10.3390/reports8040212 - 23 Oct 2025
Viewed by 85
Abstract
Background and Clinical Significance: In a single phenotypically female patient, we describe the rare co-occurrence of partial androgen insensitivity syndrome (PAIS) and congenital adrenal hyperplasia (CAH). Partial androgen insensitivity syndrome (PAIS) is one of disorder of sex development (DSD) with a 46 [...] Read more.
Background and Clinical Significance: In a single phenotypically female patient, we describe the rare co-occurrence of partial androgen insensitivity syndrome (PAIS) and congenital adrenal hyperplasia (CAH). Partial androgen insensitivity syndrome (PAIS) is one of disorder of sex development (DSD) with a 46 XY karyotype. Congenital adrenal hyperplasia (CAH) is a genetic defect in adrenal steroidogenesis. Case presentation: We present the case of a 26-year-old female patient who was observed to have abnormally formed external genitourinary organs. She was diagnosed at the neonatal period. Tests performed showed a 46 XY karyotype, an absence of sex chromatin with a weakly positive DNA test for the SRY gene, an absence of uterine primordium with the presence of male gonads in the perineal skin folds, and a urethral outlet at the base of an undeveloped genital process. The daily urinary steroid excretion profile was normal. The patient was diagnosed with partial androgen insensitivity syndrome (PAIS). As a 4-year-old child, she underwent a bilateral gonadectomy due to possible further virilization and also the risk of testicular malignancy. Despite treatment, progressive androgenization was observed, the cause of which turned out to be congenital adrenal hyperplasia (CAH) in the course of P450 oxidoreductase (POR) disorder. Conclusions: In this article, we highlight the exceptional rarity of the co-occurrence of PAIS and CAH, underscoring the need for a multidisciplinary and individualized approach in the absence of clear guidelines regarding surgical timing and gender identity. Careful clinical evaluation and ongoing observation are essential for accurate diagnosis and optimal patient care. Full article
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26 pages, 6992 KB  
Review
Endovascular Repair of Thoracic Aortic Atresia in Adults: A Narrative Review of a Rare Entity and Emerging Technique
by Claudiu Florin Rășinar, Petru Liuba, Alina Diduța Brie, Alexandru Tîrziu, Cristian Mornoș, Daniel Miron Brie, Dan Ion Gaiță and Constantin Tudor Luca
Life 2025, 15(11), 1651; https://doi.org/10.3390/life15111651 - 23 Oct 2025
Viewed by 88
Abstract
Thoracic aortic atresia in adults represents a rare and extreme manifestation of aortic coarctation, marked by complete luminal occlusion and frequently compensated by extensive collateral circulation. This narrative review critically evaluates existing literature and institutional experience concerning surgical and endovascular repair strategies for [...] Read more.
Thoracic aortic atresia in adults represents a rare and extreme manifestation of aortic coarctation, marked by complete luminal occlusion and frequently compensated by extensive collateral circulation. This narrative review critically evaluates existing literature and institutional experience concerning surgical and endovascular repair strategies for aortic atresia, synthesizing evidence from related aortic arch pathologies due to the absence of direct comparative studies. Both treatment modalities—open surgical repair and catheter-based recanalization with stenting—have evolved significantly, presenting distinct advantages and limitations influenced by patient anatomy, age, and comorbidities. While surgical repair remains the standard for neonates, infants, and complex cases due to superior long-term durability and blood pressure control, endovascular procedures using chronic total occlusion technique and covered stents offer less invasive alternatives with rapid recovery, particularly in adults with suitable anatomic characteristics. The review highlights procedural considerations, including technical approaches, stent selection, and potential complications such as restenosis, hypertension, and vascular injury. Individualized, multidisciplinary decision-making remains essential, with shared consensus guiding therapy in the absence of randomized trials. The article identifies critical gaps in knowledge, emphasizing the need for multicenter, long-term studies and technological advances—including hybrid and personalized strategies for optimal management and for improving outcomes in this challenging congenital condition. Full article
(This article belongs to the Special Issue Precision Medicine in Cardiovascular Diseases)
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18 pages, 6752 KB  
Review
ITAC and Non-ITAC Sinonasal Adenocarcinoma: Classification, Etiopathogenesis, Diagnosis and Therapy Focusing on Interdisciplinarity
by Miriam Sciacca, Federico Chillari, Stefano Pergolizzi, Valeria Venuti, Giuseppe Iatì, Silvana Parisi, Giuliana Ciappina, Fabio Minutoli, Vincenzo Fiorentino, Guido Fadda, Antonio Bottari and Giacomo Ferrantelli
Medicina 2025, 61(11), 1895; https://doi.org/10.3390/medicina61111895 - 22 Oct 2025
Viewed by 86
Abstract
Sinonasal adenocarcinomas are rare malignant tumors arising from the epithelial lining of the sinonasal tract. They are classified into intestinal-type (ITAC) and non-intestinal-type adenocarcinomas (non-ITAC), with different histopathological features, aetiologies, and prognostic outcomes. Occupational exposure, particularly to wood and leather dust, is strongly [...] Read more.
Sinonasal adenocarcinomas are rare malignant tumors arising from the epithelial lining of the sinonasal tract. They are classified into intestinal-type (ITAC) and non-intestinal-type adenocarcinomas (non-ITAC), with different histopathological features, aetiologies, and prognostic outcomes. Occupational exposure, particularly to wood and leather dust, is strongly linked to ITAC. Diagnosis requires a combination of clinical evaluation, imaging, histology, and immunohistochemical profiling. Due to the complexity of the sinonasal anatomy and the aggressive behaviour of these tumors, an early and accurate diagnosis is fundamental. Treatment usually involves surgical resection, often followed by radiotherapy, while the role of chemotherapy remains limited. This review outlines the classification, etiopathogenesis diagnosis and management strategies for sinonasal adenocarcinomas, emphasizing the importance of multidisciplinary approaches for optimal outcomes. Full article
(This article belongs to the Section Oncology)
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14 pages, 544 KB  
Systematic Review
Breastfeeding During and After Breast Cancer Diagnosis—A Systematic Review of the Literature
by Anna Ampatzi, Nikoleta Aikaterini Xixi, Rozeta Sokou, Eleni Karapati, Zoi Iliodromiti, Paraskevi Volaki, Styliani Paliatsiou, Nicoletta Iacovidou and Theodora Boutsikou
J. Clin. Med. 2025, 14(20), 7450; https://doi.org/10.3390/jcm14207450 - 21 Oct 2025
Viewed by 113
Abstract
Background/Objectives: Breast cancer diagnosis in lactating women is relatively uncommon. The term Pregnancy-Associated Breast Cancer (PABC) refers to breast cancer diagnosed during pregnancy or within the first year postpartum. There are several factors that limit the ability to breastfeed. Despite emerging evidence suggesting [...] Read more.
Background/Objectives: Breast cancer diagnosis in lactating women is relatively uncommon. The term Pregnancy-Associated Breast Cancer (PABC) refers to breast cancer diagnosed during pregnancy or within the first year postpartum. There are several factors that limit the ability to breastfeed. Despite emerging evidence suggesting that breastfeeding may be feasible and should be supported in women with PABC, there is still limited evidence regarding the percentage of them who attempt breastfeeding, and the challenges they may encounter. This study aims to systematically reviewing the literature on the available evidence regarding breastfeeding in women diagnosed with PABC. Methods: PubMed and Scopus were systematically searched for studies on breastfeeding in PABC until 26 June 2025. Data on breastfeeding outcomes and diagnostic challenges in relation to PABC were extracted. The systematic review is registered in PROSPERO (CRD420251043141). Results: A total of 15 studies met the inclusion criteria and were included in this review. The results showed a scarcity of literature regarding the percentage of women with PABC who breastfeed. Existing data revealed that a small percentage successfully breastfeed. A common occurrence throughout the studies was the concern of breastfeeding during cancer treatment. In almost all cases, reduced milk production was reported, along with the co-administration of formula as a substitute for breast milk. Conclusions: Management of women with PABC should not be limited to oncologic treatment but should also encompass structured breastfeeding counseling and multidisciplinary support, ideally within specialized breast cancer centers. Such integrated care has the potential to optimize maternal health outcomes, improve quality of life, and promote a more favorable pregnancy and postpartum experience. Full article
(This article belongs to the Section Clinical Pediatrics)
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12 pages, 1171 KB  
Article
Surgical Pulmonary Embolectomy Versus Systemic Thrombolysis in High-Risk Pulmonary Embolism: A Retrospective Single-Center Analysis
by Arash Motekallemi, Linus C. Markus Rohrwild, Jonas Ajouri, Ridvan Dryana, Tamari Tvildiani, Verena Vach, Ralf M. Muellenbach and Ali Asghar Peivandi
J. Clin. Med. 2025, 14(20), 7448; https://doi.org/10.3390/jcm14207448 - 21 Oct 2025
Viewed by 195
Abstract
Background: Pulmonary embolism (PE) is a life-threatening condition with high mortality, particularly in high-risk cases where rapid clinical deterioration is common. The optimal management strategy for high-risk PE remains debated. Systemic thrombolysis (ST) is widely used but is associated with substantial bleeding risks. [...] Read more.
Background: Pulmonary embolism (PE) is a life-threatening condition with high mortality, particularly in high-risk cases where rapid clinical deterioration is common. The optimal management strategy for high-risk PE remains debated. Systemic thrombolysis (ST) is widely used but is associated with substantial bleeding risks. Surgical pulmonary embolectomy (SPE) has re-emerged as a viable alternative, particularly in patients with contraindications to thrombolysis or failed response. However, the evidence comparing SPE and ST in critically ill patients remains limited, and current guidelines provide only limited guidance. This study aims to evaluate the outcomes between SPE and ST in critically ill patients, focusing on mortality and complication rates. Methods: This retrospective study included 96 high risk patients with severe acute pulmonary embolism treated between 2015 and 2023, with 48 undergoing SPE and 48 receiving ST who were matched 1:1 based on baseline variables and hemodynamic presentation. Outcomes assessed included in-hospital mortality, PE-related death, neurological complications, bleeding events, hospitalization duration, as well as further postinterventional complications. Results: In-hospital mortality was 16.6% in the SPE group in contrast to 25.0% in the ST group (p = 0.765). Neurological complications were significantly lower in SPE (2.1%) compared to ST (12.5%) (p = 0.05). Life-threatening hemorrhage occurred at similar rates in both groups (SPE: 18.8%, ST: 14.6%); however, non-life-threatening bleeding was more common in ST (16.7% vs. 2.1%, p = 0.014). Hospitalization duration was significantly longer for SPE patients (mean 17.4 vs. 11.4 days, p < 0.001), who also presented with more severe disease, including higher ECMO utilization. Conclusions: SPE is a safe and effective alternative to ST in PE, offering comparable mortality, fewer neurologic complication and a reduced risk of bleeding. These findings highlight the importance of individualized, risk-adapted treatment pathways and support the inclusion of SPE as a frontline consideration in the management of PE in critically ill patients in experienced centers with multidisciplinary support. Full article
(This article belongs to the Section General Surgery)
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20 pages, 543 KB  
Review
Tools for Detecting Ageing in People with Autism Spectrum Disorder: A Scoping Review
by Maider Ugartemendia-Yerobi, Beatriz Pereda-Goikoetxea, Maria Isabel Trespaderne and Jaione Lacalle
Healthcare 2025, 13(20), 2640; https://doi.org/10.3390/healthcare13202640 - 20 Oct 2025
Viewed by 126
Abstract
Background: People with Autism Spectrum Disorder (ASD) require a customised, multidisciplinary plan throughout their lifetime to support optimal health. The purpose of this scoping review was to synthesise research on the main scales used to detect signs of ageing in people with ASD. [...] Read more.
Background: People with Autism Spectrum Disorder (ASD) require a customised, multidisciplinary plan throughout their lifetime to support optimal health. The purpose of this scoping review was to synthesise research on the main scales used to detect signs of ageing in people with ASD. Methods: Eligible papers published between January 2003 and August 2025 were identified through searches of PubMed, PsycInfo, Scopus, Web of Science, NICE and Cochrane databases. The assessment was performed using the Joanna Briggs Institute critical appraisal and extraction checklist. Of the 820 papers reviewed, 24 were found to meet the established criteria. Results: Based on the evidence collected, 57 tools focusing on specific domains within the Comprehensive Geriatric Assessment were identified: 19 addressed the functional domain, 18 the mental, 6 the biomedical, 1 the social, 2 related to frailty, 1 to fall risk, and 10 to quality of life. Conclusions: This review highlights the need to obtain a ‘multi-domain’ tool for the detection of ageing in autistic people, which would facilitate the development of a Comprehensive Geriatric Assessment that makes planning customised care possible. Full article
(This article belongs to the Special Issue Nursing Care for Patients with Autism Spectrum Disorder)
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28 pages, 1015 KB  
Review
Multicentric and Multifocal Breast Tumors—Narrative Literature Review
by Mircea-Octavian Poenaru, Mihaela Amza, Cristian-Valentin Toma, Fernanda-Ecaterina Augustin, Irina Pacu, Giorgia Zampieri, Liana Ples, Romina-Marina Sima and Andrei-Sebastian Diaconescu
Cancers 2025, 17(20), 3380; https://doi.org/10.3390/cancers17203380 - 20 Oct 2025
Viewed by 341
Abstract
Background: Multifocal (MF) and multicentric (MC) breast cancers, defined by the presence of multiple synchronous tumor foci within the same breast, present important diagnostic, therapeutic, and prognostic challenges. Historically considered a contraindication for breast-conserving therapy (BCT), advances in imaging, surgical techniques, and adjuvant [...] Read more.
Background: Multifocal (MF) and multicentric (MC) breast cancers, defined by the presence of multiple synchronous tumor foci within the same breast, present important diagnostic, therapeutic, and prognostic challenges. Historically considered a contraindication for breast-conserving therapy (BCT), advances in imaging, surgical techniques, and adjuvant therapy have reshaped management strategies. Methods: A narrative literature review was conducted through PubMed, Web of Science, and Scopus, prioritizing ISI-indexed articles published within the last 10–15 years. More than 55 relevant studies, including systematic reviews, meta-analyses, and large cohorts, were analyzed to evaluate epidemiology, pathological features, imaging modalities, treatment outcomes, and prognosis of MF/MC breast cancers. Results: The reported incidence of MF/MC breast cancers ranges from 10% to 24%, increasing when MRI or whole-organ pathology is applied. MRI can detect otherwise occult additional foci in up to 30% of patients, improving staging accuracy but raising concerns of overdiagnosis. MF/MC presentation is strongly associated with lobular histology, younger age at diagnosis, and higher rates of axillary involvement—nodal positivity is observed in up to 45% of MF/MC cases versus 28% in unifocal tumors. Pathological analyses demonstrate frequent clonal origin of MF lesions, whereas MC lesions may represent independent primaries, occasionally with receptor heterogeneity that alters systemic therapy selection. From a prognostic perspective, older series suggested shorter breast cancer-specific survival (e.g., median 154 vs. 204 months for MF/MC vs. unifocal disease), and higher local recurrence with BCT. However, contemporary analyses, including a 2022 meta-analysis of 15,703 patients, demonstrated no significant difference in overall or disease-free survival once adjusted for tumor size and nodal status. Local recurrence remains slightly higher with BCT in MF/MC (5.6% vs. 4.2%), but outcomes are equivalent to mastectomy when radiotherapy is appropriately delivered. Five-year survival in early-stage MF/MC exceeds 90% with guideline-concordant multimodal therapy. Conclusions: MF/MC breast cancers represent a biologically heterogeneous entity. Optimal outcomes rely on precise imaging, complete excision, tailored systemic therapy, and multidisciplinary management, with increasing acceptance of breast conservation in selected patients. Full article
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
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14 pages, 2035 KB  
Review
Multidisciplinary Perspective of Spread Through Air Spaces in Lung Cancer: A Narrative Review
by Riccardo Orlandi, Lorenzo Bramati, Maria C. Andrisani, Giorgio A. Croci, Claudia Bareggi, Simona Castiglioni, Francesca Romboni, Sara Franzi and Davide Tosi
Cancers 2025, 17(20), 3374; https://doi.org/10.3390/cancers17203374 - 19 Oct 2025
Viewed by 294
Abstract
Spread Through Air Spaces (STAS) is an emerging pattern of tumor invasion in lung cancer, first recognized by the World Health Organization in 2015. This narrative review examines STAS from a multidisciplinary perspective, integrating pathologic, radiologic, oncologic, and surgical points of view, together [...] Read more.
Spread Through Air Spaces (STAS) is an emerging pattern of tumor invasion in lung cancer, first recognized by the World Health Organization in 2015. This narrative review examines STAS from a multidisciplinary perspective, integrating pathologic, radiologic, oncologic, and surgical points of view, together with molecular biology to assess its clinical significance, diagnostic challenges, and therapeutic implications. Pathologically, STAS is characterized by tumor cells floating beyond the main tumor, contributing to recurrence and poor prognosis. Radiologic advancements suggest potential imaging markers for STAS, such as spiculation, the absence of an air bronchogram, solid tumor components, as well as high fluorodeoxyglucose uptake, though definitive preoperative identification remains challenging. Oncologic studies link STAS to aggressive tumor behavior and lympho-vascular invasion, suggesting a role for adjuvant chemotherapy even in the earliest stages of disease; furthermore, specific molecular alterations have been discovered, including EGFR wild-type status and ALK/ROS1 rearrangements together with high Ki-67 expression, tumor necrosis, and alterations in cell adhesion proteins like E-cadherin. Surgical aspects highlight the increased risk of recurrence following limited resection, raising concerns about optimal surgical strategies. The debate over STAS as a true invasion mechanism versus an artifact from surgical handling underscores the need for standardized pathological evaluation. This review aims to refine STAS detection, integrate it into multidisciplinary treatment decision-making, and assess its potential as a staging criterion in lung cancer management. Full article
(This article belongs to the Special Issue Surgical Management of Non-Small Cell Lung Cancer)
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42 pages, 1849 KB  
Review
Recommendations on the Clinical Application and Future Potential of α-Particle Therapy: A Comprehensive Review of the Results from the SECURE Project
by Valentina Di Iorio, Anna Sarnelli, Stefano Boschi, Maddalena Sansovini, Rosa Maria Genovese, Cipriana Stefanescu, Vlad Ghizdovat, Wael Jalloul, Jennifer Young, Jane Sosabowski, Petra Kolenc, Rachel Roberts, Govert de With, Dimitris Visvikis and Renata Mikolajczak
Pharmaceuticals 2025, 18(10), 1578; https://doi.org/10.3390/ph18101578 - 18 Oct 2025
Viewed by 526
Abstract
This review comprehensively assesses the clinical applications and future potential of alpha-emitting radionuclides available for targeted alpha-particle therapy (TAT) in cancer treatment. The approval of radium-223 therapy in 2013 marked a significant advancement in alpha-emitting therapeutic radiopharmaceuticals, which are primarily used in treatment [...] Read more.
This review comprehensively assesses the clinical applications and future potential of alpha-emitting radionuclides available for targeted alpha-particle therapy (TAT) in cancer treatment. The approval of radium-223 therapy in 2013 marked a significant advancement in alpha-emitting therapeutic radiopharmaceuticals, which are primarily used in treatment of prostate cancer. The EU SECURE project was introduced as a major initiative to enhance the sustainability and safety of medical alpha-emitting radionuclides production in Europe. This literature review was conducted by a multidisciplinary team on selected radionuclides, including actinium-225, bismuth-213, astatine-211, lead-212, terbium-149, radium-223 and thorium-227. These were selected based on their clinical significance, as identified in the EU PRISMAP project and subsequent literature searches. The review process involved searching major databases using specific keywords related to alpha-emitter therapy and was limited to articles in English. For each selected radionuclide, the physical characteristics, the radiochemistry, and the pre-clinical and clinical studies are explored. Actinium-225 is the most widely studied alpha emitter, with several preclinical and clinical studies on prostate cancer and neuroendocrine tumours. Other types of tumours (such as glioblastoma) still require preclinical and clinical development. Bismuth-213 bound to antibodies, peptides and nanobodies has shown optimal results in preclinical and clinical studies, with increased median survival and no significant toxicity. Astatine-211 differs from most other α-emitters relevant to TAT, since it yields one α-particle per decay. This offers certain translational advantages, including the simplification of radiation dosimetry calculations and quality control (QC). Lead-212 has the advantage of being an in situ generator with likely widespread availability. Although clinical data are limited, the findings are promising at this stage. The unconventional production of Terbium-149 is the primary reason it has not yet progressed to clinical trials. Overcoming this production obstacle would allow more detailed preclinical investigations. Optimal results with Thorium-227-labelled agents have been observed in preclinical studies, including delays in cellular growth, multiple double-strand breaks and complete regression. Intermediate phase I trial results have also been reported, demonstrating safety and tolerability, as well as an objective response rate of 25%.: The results highlight the advantages of alpha particles in targeting cancer cells with minimal radiation to normal tissue, emphasising the need for high specificity and stability in delivery mechanisms, as well as suggesting that the full clinical potential of alpha particle therapy remains unexplored. Theranostic approach and dosimetric evaluations still represent relevant challenges. Full article
(This article belongs to the Section Radiopharmaceutical Sciences)
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12 pages, 646 KB  
Case Report
Perioperative Anesthetic Considerations in HMG-CoA Lyase Deficiency: Case Report and Literature Review
by Vasileia Nyktari, Georgios Papastratigakis, Alexandra Koulousi, Chrysi Mandola, Foteini Chaniotaki, Ioannis Goniotakis, Stavroula Ilia and Alexandra Papaioannou
J. Clin. Med. 2025, 14(20), 7332; https://doi.org/10.3390/jcm14207332 - 17 Oct 2025
Viewed by 190
Abstract
Background/Objectives: 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) is an extremely rare autosomal recessive metabolic disorder caused by mutations in the HMGCL gene. HMGCLD disrupts ketogenesis and β-oxidation, leading to energy failure during fasting or stress, with clinical episodes characterized by hypoglycemia, hyperammonemia, lactic acidosis, [...] Read more.
Background/Objectives: 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) is an extremely rare autosomal recessive metabolic disorder caused by mutations in the HMGCL gene. HMGCLD disrupts ketogenesis and β-oxidation, leading to energy failure during fasting or stress, with clinical episodes characterized by hypoglycemia, hyperammonemia, lactic acidosis, and encephalopathy. Only 211 cases have been reported worldwide, with no prior reports on anesthetic management in these patients. Methods: We report a 14.5-year-old girl with known HMGCLD who was admitted with abdominal pain and nausea following a fatty meal. Imaging confirmed acute cholecystitis. Initial conservative management failed due to persistent vomiting and inability to tolerate feeding. Deviation from the metabolic protocol led to lactic acidosis and hypoglycemia, requiring intensive care with bicarbonate, carnitine, and glucose infusion. Once optimized, she underwent emergency laparoscopic cholecystectomy under sevoflurane-based anesthesia. Propofol was avoided, given the patient’s compromised lipid metabolism. Intraoperative glucose and acid-base status were closely monitored, with balanced dextrose-based fluids. Results: The patient remained hemodynamically stable throughout and was discharged three days postoperatively. Conclusions: This case highlights the anesthetic challenges of HMGCLD, where system-level miscommunication can trigger severe metabolic decompensation. A review of the literature emphasizes fasting avoidance, continuous glucose supplementation, careful drug and fluid selection, and multidisciplinary coordination. This report provides the first anesthetic roadmap for HMGCLD, underscoring the need for individualized care and meticulous perioperative metabolic control. Full article
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Review
Advances in the Multimodal Management of Pediatric Arteriovenous Malformations: A 10-Year Review
by Ammar Saloum, Yusor Al-Nuaimy, Denise Baloi, Michael Karsy, Mehrdad Pahlevani and Brandon Lucke-Wold
Life 2025, 15(10), 1620; https://doi.org/10.3390/life15101620 - 17 Oct 2025
Viewed by 272
Abstract
Pediatric brain arteriovenous malformations (AVMs) are rare but high-risk vascular anomalies associated with substantial morbidity and mortality due to their elevated lifetime risk of rupture. Over the past decade, advances in microsurgical resection, stereotactic radiosurgery (SRS), and endovascular embolization have reshaped the management [...] Read more.
Pediatric brain arteriovenous malformations (AVMs) are rare but high-risk vascular anomalies associated with substantial morbidity and mortality due to their elevated lifetime risk of rupture. Over the past decade, advances in microsurgical resection, stereotactic radiosurgery (SRS), and endovascular embolization have reshaped the management landscape, yet treatment remains highly individualized and controversial, especially in unruptured cases. This narrative review synthesizes findings from 20 eligible studies published between 2015 and 2025, examining outcomes across different modalities. Microsurgical resection demonstrated the highest immediate obliteration rates (>95%) in low-grade, accessible, ruptured lesions, but recurrence rates remain disproportionately higher in children (up to 29%). SRS achieved obliteration rates of 63–72% in Spetzler–Martin (SM) I–III lesions with low complication and recurrence rates, although outcomes were less favorable for higher-grade AVMs. Embolization alone provided limited curative potential but served as an important adjunct in multimodal therapy. Importantly, embolization prior to radiosurgery was associated with reduced obliteration rates and higher complication risks. Across modalities, hemorrhagic presentation often predicted better treatment response, while recurrence and long-term surveillance emerged as central challenges in pediatric care. These findings highlight the necessity of multidisciplinary, individualized management strategies and emphasize the importance of lifelong follow-up to mitigate recurrence risk and optimize outcomes. Full article
(This article belongs to the Section Medical Research)
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